Nonmelanoma skin cancer is the most frequent malignancy, with an incidence exceeding that of all noncutaneous malignancies combined. The conventional goal of therapy is removal of the primary cancer and prevention of its recurrence, a long-term outcome that cannot be assessed adequately before five years after therapy. For most tumors, many therapies can prevent recurrence, and although therapies vary in cost, existing data are insufficient to permit evidence-based choices among therapies. We have assembled and followed a consecutive cohort of patients with nonmelanoma skin cancer (NMSC) to determine their short- term, patient-reported outcomes. We have learned that two therapies that vary widely in cost and are used differently in different settings nonetheless have similar in short-term outcomes, including quality-of-life. This project will build on this previous work, by determining long-term outcomes, including tumor recurrence. Objective and Specific Aims. To determine the effectiveness of therapies for nonmelanoma skin cancer by comparing long-term tumor recurrence rates and quality of life after treatments. This application proposes a prospective longitudinal study of a cohort of patients assembled at the time of diagnosis of NMSC. The cohort consists of all 1545 patients with new primary NMSC diagnosed in 1999-2000 at two large dermatology practices. In this project we will compare outcomes from the three most common therapies, tumor destruction with electrodessication & curettage, excision, and Mohs surgery. The primary outcome is tumor recurrence at a minimum of five years after therapy; a secondary outcome is skin-related quality of life. We hypothesize that tumor recurrence will be highest after electrodessication & curettage, and similar after excision and Mohs surgery. Principal sources of data are patient examination, medical records, and patient responses to surveys. Analyses. Mixed effects generalized linear models will be used to model the effect of treatment on outcomes, adjusting for patient, tumor, and clinician factors that might likely have affected tumor recurrence and quality of life at five years after therapy. Multivariate Cox proportional hazards models will also be used to explore the distribution of time to detection of first tumor recurrence. Relevance to Public Health. Given the high prevalence of NMSC, effectiveness of therapies is important, but poorly understood. This project will evaluate effectiveness of therapies in preventing tumor recurrence and improving quality of life in a valuable consecutive cohort on whom high-fidelity baseline clinical and patient-reported data are available. Results will inform clinicians by permitting therapeutic choices that are more directly based on evidence. The results will also provide a basis for planning controlled trials of different treatments of NMSC, to guide decisions about the use of resources for this common tumor.